Hydrochloric Acid → (2E)-3-{4-[({1-[({3-cyclohexyl-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2-phenyl-1H-indol-6-yl}carbonyl)amino]cyclopentyl}carbonyl)amino]phenyl}acrylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 3-cyclohexyl-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-2-phenyl-1H-indole-6-carboxylic acid (from Step 4) in DMF (0.1 M) was treated with DIPEA (4 eq.), HATU (1.5 eq.) and ethyl (2E)-3-(4-{[(1-aminocyclopentyl)carbonyl]amino}phenyl)acrylate (1.1 eq, prepared as described in Example 1, Step 7). The solution was stirred at 25° C. overnight. The mixture was diluted with EtOAc, and then washed sequentially with HCl (2×, 1N), saturated aqueous NaHCO3 (2×) and brine. The organic layer was dried over Na2SO4 and concentrated to afford an oil, which was dissolved in a mixture of THF/MeOH/H2O (0.05 M, 4:1:1, v/v/v). LiOH monohydrate (1.3 eq.) was added and the resultant mixture stirred at 40° C. for 5 h. The reaction mixture was acidified with HCl (1N) and purified by RP-HPLC (column: Waters X-terra C18, 19×150 mm, 5 micron; flow 17 mL/min) to give the title compound (20%) as a white powder after lyophilization.

Provenance & Evidence